Mutagenetix > Incidental Mutations

Incidental Mutation 'R7039:Epha4'

546908

Institutional Source

Beutler Lab

Gene Symbol

Epha4

Ensembl Gene

ENSMUSG00000026235

Gene Name

Eph receptor A4

Synonyms

rb, Sek, Sek1, 2900005C20Rik, Cek8, Hek8, Tyro1

MMRRC Submission

Accession Numbers

Genbank: NM_007936; MGI: 98277

Is this an essential gene?

Probably essential (E-score: 0.927) question?

Stock #

R7039 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

77367185-77515088 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 77506785 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 196 (S196P)

Ref Sequence

ENSEMBL: ENSMUSP00000139640 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000027451] [ENSMUST00000186930] [ENSMUST00000188797] [ENSMUST00000188952] [ENSMUST00000190149]

PDB Structure

THE CRYSTAL STRUCTURE OF AN EPH RECEPTOR SAM DOMAIN REVEALS A MECHANISM FOR MODULAR DIMERIZATION. [X-RAY DIFFRACTION]
Crystal structure of a mutant EphA4 kinase domain (Y742A) [X-RAY DIFFRACTION]
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Crystal structure of EphA4 kinase domain in complex with VUF 12058 [X-RAY DIFFRACTION]
CRYSTAL STRUCTURE OF EPHA4 KINASE DOMAIN [X-RAY DIFFRACTION]
Crystal structure of EphA4 kinase domain in complex with Dasatinib. [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000027451
AA Change: S196P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000027451
Gene: ENSMUSG00000026235
AA Change: S196P

Domain	Start	End	E-Value	Type
EPH_lbd	30	204	1.35e-128	SMART
FN3	329	420	1.94e-8	SMART
FN3	441	522	9.18e-10	SMART
Pfam:EphA2_TM	548	618	1.7e-24	PFAM
TyrKc	621	878	1.91e-134	SMART
SAM	908	975	1.96e-20	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000186930

SMART Domains

Protein: ENSMUSP00000140370
Gene: ENSMUSG00000026235

Domain	Start	End	E-Value	Type
signal peptide	1	19	N/A	INTRINSIC
FN3	33	124	9.6e-11	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000188797
AA Change: S196P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000140954
Gene: ENSMUSG00000026235
AA Change: S196P

Domain	Start	End	E-Value	Type
EPH_lbd	30	204	1.35e-128	SMART
FN3	329	420	1.94e-8	SMART
FN3	441	522	9.18e-10	SMART
Pfam:EphA2_TM	547	618	1.8e-27	PFAM
TyrKc	621	878	1.91e-134	SMART
SAM	908	975	1.96e-20	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000188952
AA Change: S196P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000139640
Gene: ENSMUSG00000026235
AA Change: S196P

Domain	Start	End	E-Value	Type
EPH_lbd	30	204	1.35e-128	SMART
FN3	329	420	1.94e-8	SMART
FN3	441	522	9.18e-10	SMART
Pfam:EphA2_TM	547	618	1.8e-27	PFAM
TyrKc	621	878	1.91e-134	SMART
SAM	908	975	1.96e-20	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000190149

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
PHENOTYPE: Mutants are known for their "hopping gait". Homozygotes for targeted null mutations show loss of limb alternation in locomotion and axon guidance defects of the corticospinal tract within medulla and spinal cord, resulting in aberrant midline projections. Heterozygotes show less severe phenotype. [provided by MGI curators]

Allele List at MGI

All alleles(66) : Targeted, knock-out(3) Targeted, other(9) Gene trapped(52) Spontaneous(2)

Other mutations in this stock

Total: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9530053A07Rik	G	A	7: 28,140,148	R462Q	possibly damaging	Het
Actl7b	A	T	4: 56,741,022	L112Q	probably damaging	Het
Agap3	A	C	5: 24,483,401	I396L	probably benign	Het
AI987944	G	T	7: 41,374,456	S366R	probably benign	Het
Aox3	A	G	1: 58,176,555	T1049A	probably damaging	Het
Ap1g2	A	T	14: 55,102,654	L407*	probably null	Het
Baiap3	G	A	17: 25,243,840	R1075C	probably benign	Het
Brd3	T	C	2: 27,456,917	K402E	probably damaging	Het
Cc2d2b	A	T	19: 40,802,401	D935V	probably damaging	Het
Cenpe	A	G	3: 135,255,456	N1904D	probably benign	Het
Cfap74	G	T	4: 155,454,108		probably null	Het
Chrdl2	A	G	7: 100,028,672	T261A	probably damaging	Het
Cyp4a14	G	A	4: 115,491,081	R400C	probably benign	Het
Dhfr	G	A	13: 92,355,283	V9I	probably benign	Het
Evc2	T	A	5: 37,421,888	L1115Q	probably damaging	Het
Fat3	T	A	9: 16,376,265	E654V	probably damaging	Het
Fer1l4	C	T	2: 156,036,730	V14I	probably benign	Het
Frmd5	A	T	2: 121,547,647		probably benign	Het
Helz	T	C	11: 107,619,318		probably null	Het
Igkv6-13	T	C	6: 70,457,514	S116G	probably benign	Het
Iscu	T	C	5: 113,776,772	V115A	possibly damaging	Het
Jade2	C	A	11: 51,828,359	K253N	probably damaging	Het
Katnal2	A	G	18: 77,047,172		probably null	Het
Kif13a	C	T	13: 46,752,455	V671M	possibly damaging	Het
Magi3	T	C	3: 104,051,383	D462G	probably damaging	Het
Map3k14	T	C	11: 103,221,035	N940S	probably damaging	Het
Masp2	A	T	4: 148,602,586	M1L	probably benign	Het
Mga	G	A	2: 119,932,678	V1272I	probably benign	Het
Mib2	T	C	4: 155,659,701	D168G	probably damaging	Het
Mmp1a	TG	TGG	9: 7,465,083		probably null	Het
Msto1	A	C	3: 88,911,390	V287G	probably damaging	Het
Myo5b	T	A	18: 74,701,528	D886E	probably benign	Het
Nek10	T	C	14: 14,826,946	I48T	possibly damaging	Het
Nek10	A	T	14: 14,986,700	R1013W	probably damaging	Het
Nipsnap3a	T	C	4: 53,000,130	V194A	probably damaging	Het
Nlrp9a	A	T	7: 26,567,942	T766S	probably benign	Het
Nol10	T	A	12: 17,429,184	S672T	possibly damaging	Het
Olfr1062	A	T	2: 86,422,833	I281K	possibly damaging	Het
Olfr1226	A	T	2: 89,193,446	I196N	probably damaging	Het
Olfr1253	A	T	2: 89,752,751	F26I	probably benign	Het
Olfr933	T	A	9: 38,975,987	F104I	probably damaging	Het
Patj	T	A	4: 98,569,078	N1272K	probably damaging	Het
Peak1	T	C	9: 56,257,809	E945G	probably benign	Het
Peg3	C	T	7: 6,717,859	D16N	probably damaging	Het
Pik3r4	T	G	9: 105,676,890	I1082M	possibly damaging	Het
Plekhg5	T	A	4: 152,107,785	M472K	possibly damaging	Het
Plekhm1	T	C	11: 103,395,228	D127G	probably damaging	Het
Ppfia4	G	A	1: 134,312,115	S908L	probably damaging	Het
Psmc3	A	G	2: 91,055,046	N60S	probably benign	Het
Rapgef1	T	A	2: 29,726,214	D697E	probably damaging	Het
Rapgef3	T	A	15: 97,761,568	H54L	probably benign	Het
Rhobtb3	G	A	13: 75,872,453	R577*	probably null	Het
Safb2	T	C	17: 56,564,594	E218G	possibly damaging	Het
Scaf1	C	T	7: 45,008,426	R343H	probably damaging	Het
Snx24	G	A	18: 53,340,235		probably null	Het
Tbc1d1	T	C	5: 64,284,757	F707L	probably benign	Het
Tcaf2	T	C	6: 42,626,140	T829A	probably damaging	Het
Tcea2	C	T	2: 181,686,918	Q248*	probably null	Het
Tcirg1	A	T	19: 3,896,666	L729Q	probably damaging	Het
Thap3	A	G	4: 151,985,692	F82L	probably damaging	Het
Ttk	T	A	9: 83,868,092	M700K	probably damaging	Het
Ubap2l	G	T	3: 90,002,355	P56H	probably damaging	Het
Ubr2	A	G	17: 47,010,213	S3P	probably benign	Het
Uchl3	C	T	14: 101,685,692		probably benign	Het
Vmn2r111	T	A	17: 22,548,184	E777D	probably damaging	Het
Vmn2r20	A	T	6: 123,386,123	D567E	probably damaging	Het
Vps13c	T	G	9: 67,937,763	L2043R	probably damaging	Het
Zan	T	G	5: 137,400,134	D4212A	unknown	Het
Zap70	C	T	1: 36,778,751	P278S	probably benign	Het
Zbtb8b	A	T	4: 129,427,685	M461K	possibly damaging	Het
Zfat	T	G	15: 68,180,362	I528L	probably benign	Het
Zfp532	T	G	18: 65,638,763	V784G	probably benign	Het

Other mutations in Epha4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01315:Epha4	APN	1	77398557	missense	probably benign	0.00
IGL01350:Epha4	APN	1	77506855	missense	probably damaging	1.00
IGL01657:Epha4	APN	1	77426838	missense	probably damaging	1.00
IGL01872:Epha4	APN	1	77383039	missense	probably benign	0.03
IGL02366:Epha4	APN	1	77426711	nonsense	probably null
IGL02426:Epha4	APN	1	77444877	missense	probably benign	0.01
IGL02428:Epha4	APN	1	77506748	missense	possibly damaging	0.94
IGL02706:Epha4	APN	1	77426845	missense	probably damaging	1.00
IGL02716:Epha4	APN	1	77380965	missense	probably damaging	1.00
IGL03348:Epha4	APN	1	77507172	missense	possibly damaging	0.82
frog	UTSW	1	77481076	intron	probably benign
R0324:Epha4	UTSW	1	77383551	missense	probably damaging	1.00
R0392:Epha4	UTSW	1	77506973	missense	probably benign	0.00
R0538:Epha4	UTSW	1	77388541	missense	probably damaging	1.00
R0562:Epha4	UTSW	1	77388487	missense	probably benign	0.00
R0885:Epha4	UTSW	1	77382939	missense	probably damaging	0.99
R1509:Epha4	UTSW	1	77380886	missense	probably damaging	1.00
R1620:Epha4	UTSW	1	77374926	missense	probably benign	0.31
R1624:Epha4	UTSW	1	77399692	missense	probably damaging	1.00
R1654:Epha4	UTSW	1	77374768	splice site	probably null
R1755:Epha4	UTSW	1	77387823	missense	probably damaging	1.00
R1807:Epha4	UTSW	1	77374904	missense	probably benign	0.05
R2046:Epha4	UTSW	1	77507162	missense	probably damaging	1.00
R2504:Epha4	UTSW	1	77382991	missense	probably damaging	1.00
R2509:Epha4	UTSW	1	77511702	missense	possibly damaging	0.84
R2511:Epha4	UTSW	1	77511702	missense	possibly damaging	0.84
R3441:Epha4	UTSW	1	77426696	missense	possibly damaging	0.90
R3724:Epha4	UTSW	1	77426543	splice site	probably benign
R3901:Epha4	UTSW	1	77380902	missense	probably damaging	1.00
R3950:Epha4	UTSW	1	77399716	missense	probably damaging	1.00
R3951:Epha4	UTSW	1	77399716	missense	probably damaging	1.00
R3952:Epha4	UTSW	1	77399716	missense	probably damaging	1.00
R4012:Epha4	UTSW	1	77390094	splice site	probably benign
R4321:Epha4	UTSW	1	77507213	critical splice acceptor site	probably null
R4422:Epha4	UTSW	1	77511717	missense	probably damaging	0.99
R4898:Epha4	UTSW	1	77390075	nonsense	probably null
R5072:Epha4	UTSW	1	77445002	missense	probably damaging	1.00
R5270:Epha4	UTSW	1	77506607	missense	probably damaging	1.00
R5281:Epha4	UTSW	1	77374867	missense	probably benign
R5315:Epha4	UTSW	1	77388472	critical splice donor site	probably null
R5531:Epha4	UTSW	1	77374876	missense	probably benign
R5621:Epha4	UTSW	1	77515049	utr 5 prime	probably benign
R5648:Epha4	UTSW	1	77398525	missense	probably benign	0.25
R5747:Epha4	UTSW	1	77506883	missense	probably damaging	0.99
R5829:Epha4	UTSW	1	77444994	missense	probably benign	0.01
R6185:Epha4	UTSW	1	77507106	missense	probably damaging	1.00
R6486:Epha4	UTSW	1	77383549	missense	probably damaging	1.00
R6821:Epha4	UTSW	1	77382945	missense	possibly damaging	0.88
R6978:Epha4	UTSW	1	77377583	missense	probably damaging	1.00
R7216:Epha4	UTSW	1	77444984	missense	probably damaging	1.00
R7270:Epha4	UTSW	1	77399785	missense	probably damaging	1.00
R7444:Epha4	UTSW	1	77387916	missense	probably damaging	1.00
R7737:Epha4	UTSW	1	77381012	missense	probably damaging	1.00
R7763:Epha4	UTSW	1	77390031	critical splice donor site	probably null
R7950:Epha4	UTSW	1	77507196	missense	probably damaging	0.99
R8297:Epha4	UTSW	1	77506910	missense	probably damaging	1.00
R8373:Epha4	UTSW	1	77507079	missense	possibly damaging	0.60
R8429:Epha4	UTSW	1	77390036	missense	probably benign	0.08
Z1088:Epha4	UTSW	1	77506662	missense	possibly damaging	0.61
Z1176:Epha4	UTSW	1	77373733	makesense	probably null
Z1176:Epha4	UTSW	1	77383011	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GTACCAGCCATTCACCATCTG -3'
(R):5'- TGCAAGGAGACGTTTAACCTC -3'

Sequencing Primer
(F):5'- GCCCCACAGTACATTTTTGG -3'
(R):5'- CTTCATCAGAGAGAGCCAGTTTG -3'

Posted On

2019-05-13